It is very difficult to measure small local magnetic fields, on the one hand because the magnetic field strength to be measured is very small, while on the other hand fields such as these also frequently decay very quickly. If the fields are produced by very small particles, they in consequence cause only a negligibly small signal on a flat sensor whose area is typically very much larger than the particle diameter.
Magnetic fields with a very low field strength are produced, for example, by magnetic beads (beads=small balls)—referred to in the following text as magnetic beads—which are used in particular in the course of biotechnological DNA investigations. In the case of DNA investigations, biological receptacles, that is to say in particular cells, the DNA, must first of all be isolated and must be multiplied before analysis, which is carried out by way of a PCR (PCR=Polymerase Chain Reaction). During this process, the magnetic beads can be used to bind the isolated DNA.
DNA isolation is frequently used in nucleic acid analysis, for example of white blood cells from full blood, in order to answer, for example, human-genome questions. For this purpose, the cells must first of all be broken open (so-called lysis) in a sample preparation step, in order to isolate the released DNA in the above sense. Blood components such as hemoglobin, immunoglobulins and lactoferrin, which can inhibit the subsequent PCR, must be removed during this process.
In the laboratory, the cells are normally unlocked using an alkaline solution (NaOH), and the DNA is then bound to the magnetic beads, which are coated with silica. A DNA string thus adheres to the silicon layer on the magnetic bead, and is fixed in this way. The magnetic beads themselves can then be isolated, as is known by way of example from German patent application DE 10 2004 050 575 A1, from the same applicant, which was not published prior to this.
In addition to the joint isolation of a large number of magnetic beads by way of a magnetic field which is applied externally to the suspension containing the magnetic beads, it is also possible to use a DNA sensor to trap a magnetic bead to which a DNA string is bound, on which DNA sensor a complementary DNA string is arranged, which combines with the DNA string on the bead side. However, this is the case only when the sequences of the heterocylic nuclear bases of both strings correspond to one another, so that recombination can occur. A large number of individual DNA strings are, of course, provided in a distributed form over the sensor area on a DNA sensor such as this so that magnetic beads with DNA can be trapped at a large number of catchment points distributed over the sensor area.
One problem in this case is to detect whether there is or is not a magnetic bead now at a catchment point. As mentioned in the introduction, a magnetic bead represents a magnetic particle which produces an extremely small magnetic field so that—seen over the area—the detectable field inhomogeneity is extremely low, and the difficulties mentioned initially of locally resolved magnetic field measurement occur.
US 2005/0 127 916 A1 discloses a method for measurement of local magnetic fields, in which GMR measurement elements are used, in particular, as sensors. GMR measurement elements such as these are described in detail, for example, in DE 196 49 265 A1, in which, in particular, a double-layer system forms a reference layer and a reference layer composed of soft-magnetic material is present. Furthermore, WO 2005/010 543 A1 discloses a magnetic measurement device which is intended to be particularly suitable for detection of magnetic nanoparticles. In this case, suitable devices/methods are used to prevent crosstalk between the signals from the sensor and those from the magnetic-field generator. Finally, US 2005/087 000 A1 discloses a sensor such as this which, in particular, is intended to be suitable for DNA analysis by way of magnetic beads.